Antimalarial drug resistance and population structure of Plasmodium falciparum in Mozambique using genomic surveillance at health facilities in 2021 and 2022.

Monitoring the emergence and spread of drug-resistant parasites is essential for effective malaria control. Here, we describe the prevalence of genetic markers of Plasmodium falciparum antimalarial drug resistance and parasite population structure in Mozambique. Drug resistance loci and microhaplotypes were genotyped by multiplex targeted amplicon sequencing of 1146 P. falciparum samples collected in 2021 (n = 321) and 2022 (n = 825 rainy season, and n = 155 dry season). pfpm2 gene copy number (associated to piperaquine resistance) was assessed using real-time quantitative PCR. No pfk13 markers of partial artemisinin resistance nor pfpm2 duplications were observed. Prevalence of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine (SP) resistance was high across all regions (> 92.5% in 2021 and > 87.8% in 2022), but pfdhps-A581G mutation was rare (1.6% in 2021 and 0.8% 2022). Both prevalence of mutations in pfdhps-436 (p < 0.001) and genetic complexity of infections increased from South to North. These results support the continued use of artemisinin-based combination therapies in Mozambique, call for a close monitoring of chemopreventive efficacy based on SP, and confirm the spatial genetic distinction in P. falciparum population observed across the country.